Tyrosine residues 654 and 670 in β-catenin are crucial in regulation of Met–β-catenin interactions

Zeng, Gang; Apte, Udayan; Micsenyi, Amanda; Bell, Aaron; Monga, Satdarshan P.

doi:10.1016/j.yexcr.2006.08.003

Cited by 83 publications

(71 citation statements)

References 38 publications

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“…One possibility is that these mutations augment a direct biochemical interaction between MET and ␤-catenin. Indeed, MET has been reported to directly phosphorylate ␤-catenin, thereby facilitating its activation (24,25). However, the mutations described here are known to independently activate ␤-catenin, so it seems just as likely that signaling from Met and ␤-catenin are independent variables that cooperate in tumorigenesis for reasons as yet unknown.…”

Section: Discussionmentioning

confidence: 87%

Distinct pathways of genomic progression to benign and malignant tumors of the liver

Tward¹,

Jones²,

Yant

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

191

187

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We used several of the genetic lesions commonly associated with human liver tumors to reconstruct genetic progression to hepatocellular carcinoma and adenoma in mouse models. We initiated tumorigenesis with a transgene of the protooncogene MET or by hydrodynamic transfection of MET in combination with other genes into the livers of adult animals. Hepatocellular carcinoma in both instances arose from cooperation between MET and constitutively active versions of ␤-catenin. In contrast, adenomas were produced by cooperation between MET and defective signaling through the transcription factor HNF1␣. Prompted by these findings, we uncovered a coincidence between activation of the protein-tyrosine kinase encoded by MET and activating mutations of ␤-catenin in a subset of human hepatocellular carcinomas. Inactivation of MET transgenes led to regression of hepatocellular carcinomas despite the persistence of activated ␤-catenin. The tumors eventually recurred in the absence of MET expression, however, presumably after the occurrence of one or more events that cooperated with activated ␤-catenin in lieu of MET. These results offer insight into hepatic tumorigenesis, provide mouse models that should be useful in the further study of hepatic tumorigenesis and for preclinical testing, and identify a subset of human hepatocellular carcinomas that may be susceptible to combination therapy directed against Met and the Wnt signaling pathway.␤-catenin ͉ hepatocyte nuclear factor 1␣ ͉ liver cancer ͉ MET ͉ mouse ͉ hepatocellular carcinoma

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Section: Discussionmentioning

confidence: 87%

Distinct pathways of genomic progression to benign and malignant tumors of the liver

Tward¹,

Jones²,

Yant

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

191

187

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“…We were the first to report temporal expression of ␤-catenin during mouse liver development with high levels at embryonic day 10 (E10)-E14 along with its nuclear/cytoplasmic location in hepatoblasts, which correlated with increased cell proliferation. 6,12 When whole livers from E10 were cultured with antisense oligonucleotides against the ␤-catenin gene (CTNNB1), a noteworthy decrease occurred in ␤-catenin protein, cell proliferation, and survival. 13 Conversely, overexpression of constitutively active ␤-catenin in the developing liver was shown to lead to a threefold increase in liver size and an expansion of the hepatocyte precursor cell population.…”

Section: Role Of ␤-Catenin In Prenatal Liver Developmentmentioning

confidence: 99%

“…6 Other reports have identified tyrosine 142 to be effected by the HGF/Met signaling in a kidney fibroblast cell line. 7 However, this residue had no role in HGF-induced mitogenesis in hepatocytes and may highlight tissue or functional specificity of these interactions.…”

mentioning

confidence: 97%

WNT/β‐catenin signaling in liver health and disease

2007

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Wnt/␤-catenin signaling is emerging as a forerunner for its critical roles in many facets of human biology. Its roles in embryogenesis, organogenesis, and maintaining tissue and organ homeostasis demonstrate its munificent character. Its roles in pathological conditions such as cancer and other human disorders such as inflammatory disorders and fibrosis reveal its villainous disposition. In liver, it also maintains its dual personality and is clearly of essence in several physiological events such as development, regeneration, and growth. Its aberrant activation is also evident in many different tumors of the liver, and recent studies are beginning to identify its role in additional hepatic pathological conditions. It is contributing to liver physiology and pathology by regulating various basic cellular events, including differentiation, proliferation, survival, oxidative stress, morphogenesis, and others. This review discusses the contribution of the Wnt/␤-catenin signaling pathway in these events and simultaneously provides an essential overview of the major developments in the field of Wnt/␤-catenin and liver pathobiology. In addition, areas that are currently deficient or understudied are identified and discussed along with the avenues of translational and clinical relevance. (HEPATOLOGY 2007;45:1298-1305

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“…Certain receptor tyrosine kinases (e.g. EGFR and Met) can synergize with Wnt/␤-catenin signaling, possibly by directly phosphorylating tyrosine residues in ␤-catenin (Brembeck et al, 2004;Bustos et al, 2006;Coluccia et al, 2007;Roura et al, 1999;Zeng et al, 2006), and thus skewing its role towards transcriptional activation. ␤-catenin Y142 (Fig.…”

Section: ␤-Catenin At Adherens Junctionsmentioning

confidence: 99%

Mechanistic insights from structural studies of β-catenin and its binding partners

Xu¹,

Kimelman

2007

Journal of Cell Science

226

217

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β-catenin is both a crucial regulator of cell adhesion and the central effector of the canonical Wnt signaling pathway. It functions as a protein organizer by interacting with numerous partners at the membrane, in the cytosol, and in the nucleus. Recent structural and biochemical studies have revealed how β-catenin engages in critical protein-protein interactions by using its armadillo repeat region and its N- and C-terminal domains. The groove in the armadillo repeat region is a particularly interesting feature of β-catenin, since it serves as a common binding site for several β-catenin-binding partners, with steric hindrance limiting which partners can be bound at a specific time. These studies provide important insights into β-catenin-mediated mechanisms of cell adhesion and Wnt signaling and suggest potential approaches for the design of therapeutic agents to treat diseases caused by misregulated β-catenin expression.

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Tyrosine residues 654 and 670 in β-catenin are crucial in regulation of Met–β-catenin interactions

Cited by 83 publications

References 38 publications

Distinct pathways of genomic progression to benign and malignant tumors of the liver

Distinct pathways of genomic progression to benign and malignant tumors of the liver

WNT/β‐catenin signaling in liver health and disease

Mechanistic insights from structural studies of β-catenin and its binding partners

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